Drugs of Unit 3 in random order Flashcards
Disopyramide
Tx: Arrythmias (Class Ia)
Mech: Na channel blocker
- Even stronger antivagal effects (than quinidine)
SE:
- Antimuscarinic effects (opposite of DUMBBELS)
- Wouldn’t use w/ glaucoma pts
Sotalol
Tx: arrytmhias (Class III)
Mech: K+ channel blocker
Also a beta blocker
Heparin
Tx: Anticoagulant
Mech: Heparin binds to anti-thrombin (protease inhib) and increases its affinity for clotting factors by 1000x
Low doses: inhibits Xa, decreasing formation of thrombin
High doses: inhibits thrombin and irreversibly binds to IXa, XIa, and XIIa
Heparin inhibits clotting in vivo and in vitro
Activates lipoprotein lipases in blood
Where we get it: located in mast cells
Harvest it from cow lung and pig intestines
Strong neg charge
Not synthetic-each batch tested individually
Pharmacokinetics: IV or subQ
Too large to be absorbed in GI tract or pass placenta
Not risk free in pregnancy though
Immediate onset–T1/2=1 hour
Degradation via heparinase
Can bind to variety of proteins so dose response in unpredictable
_Toxicity: _
- Generally non toxic
- Major danger is bleeding
- Overdose treated w/ protamine sulfate
- Strong pos charge binds w/ strong neg of heparin
- Long term use can lead to
- Osteoporosis-act. osteoclasts
- Thrombocytopenia-loss of platelets
- HIT-heparin induced thrombocytopenia
- Hypersensitivity-rare but we are injecting animal products
Isosorbide dinitrate
Tx: Angina
Slow release nitrate formulation
Can be given orally
Slow enough that effects occur before 1st pass metabolism
“-afils”
Sildenafil
Vardenafil
Tadalafil
Avanafil
Tx: ED
Mech:
- Inhibits type 5 cGMP phosphodiesterase
- Nitrates→NO→cGMP→smooth m relax
- cGMP degraded to 5’GMP via type 5 cGMP phosphodiesterase
- Relaxes arteries in corpus cavernosum→increase BF
SE:
- Slight drop in BP
- Do not use w/ alpha 1 blockers or nitrates
- Too much drop in BP
- Stroke
- MI (may be due to activity)
- Visual disturbances
- Impaired blue/green color discrimination
- NAION-some potential for damage to retina induced by cGMP PDE inhibitors
Metabolism: P450
Calcium chelators
Citric acid (in blood transfusion bags(
ADTA
EGTA
Tx: Anticoagulants
Mech: Chelate Ca
Remove Ca from clotting cascade (4 steps need Ca)
We don’t give these to people b/c Ca is involed w/ lots of mechanisms
Fondaparinux
Tx: Anticoagulant
Synthetic heparin like drug
T1/2=17 hrs
Acts only on Xa
Can cross placenta
Can’t bind protamine
Given SubQ
Warfarin
Tx: Anticoagulant
Mech:
- Vit K analog–*Koagulation*
- Inhibits enzyme that allows vit K to be recycled
- Leads to vit K deficiency
- Vit K is essential for factors 7, 9, 10 and prothrombin
- Works indirectly-doesn’t directly block clotting cascade
Route: Oral
Pharmacokinetics:
- Factor T1/2s (hrs)
- VII–6
- IX–24
- X–40
- II–60
- So 5-6 T1/2s for 99% to be gone
- 30-36 hrs
- So initial onset is 24+ hours
- Metabolism
- P450
- Lots of drug interactions
- Phenytoin/barbituates vs grapefruit juice, etc.
- Diet interactions
- Lots of Vit K in green veggies
Toxicity:
- Overdose-tx w/ Vit K
- Hemorrhage
- Can pass placenta-preg. category X
“-kinase”s
Streptokinase
Urokinase
Tx: Thrombolytic agent
(dissolve formed clots)
Mech:
- Urine plasminogen activator=Enzyme activator
- Plasminogen→plasmin
- Plasmin:
- hydrolyzes fibrin
- degrades fibrinogen
- degrades factors V and VII
Route: IV
SE: May prolong bleeding time
Deferoxamine
Tx: Acute iron OD
Mech: Iron chelator
De-Fer-oxamine
_De_toxes _Fer_rous overdose
Esmolol
Tx: arrythmias (Class II)
Mech: B1 blocker
More rapid onset of action
SE:
- Bradycardia
- Hypotension
- B2 effects-asthma
Adenosine
Tx:
- Arrythmias (Other class)
- Atrial Tachycardia
Mech:
- Binds to adenosine receptor
- Decreases firing rate of AV node
- Coronary vasodilator
Kinetics-Very short T1/2=10sec
Eptifibatide
Tx: Anticoagulant
Mech: Platelet inhibitor
Fibrinogen receptor blocker on platelet (GPIIB/IIIA receptor)
Clinical use: Decrease white thrombi
Used for coronary operation
Route: IV
SE: Thromobocytopenia
Gemfibrozil
Tx: Hyperlipidemia
Mech: Bind to PPAR-peroxisome proliferation acting receptor
Effects
- Increase transcription of LPLase
- Decrease VLDL
- Decrease Trig.
SE:
- GI upset-nausea, vomiting
- Can displace warfarin from plasma binding sites
“Choles- or coles-“
Cholestyramine
Colestipol
Coleselevam
Tx: Hyperlipidemia
Mech: Irreversibly binds bile acids in gut→choles. excreted
Effects:
- Decrease circulating cholesterol
- Increase LDL receptor
Combine w/ statins for additional decrease in LPs
SE:
- No systemic SE-too big to be absorbed
- Can bind drugs
- Digoxin
- Oral anti-coagulants
- Decrease absorption of fat soluble vitamins
- GI upset-nausea
Tissue plasminogen activator (TPA)
Tx: Thrombolytic agent
(dissolve formed clots)
Mech:
- Urine plasminogen activator=Enzyme activator
- Plasminogen→plasmin
- Plasmin:
- hydrolyzes fibrin
- degrades fibrinogen
- degrades factors V and VII
Route: IV
SE: May prolong bleeding time
Diltiazem
Tx: Arrythmias except vent. arrythmias (class IV)
Mech: Ca channel blockers
Increase refractory period
Lidocaine
Tx: arrythmias (Class Ib)
*also LA
Mech: Na channel blocker
Route: Given IV
Kinetics: First pass effect
Toxicity: Low
SE:
- Less likely to cause arrythmias but can enter CNS
- Tremors
- Seizures
Argatroban
Tx: Anticoagulant
Peptide from hirudin-diff structure, similar mech
Clinical use: when patient has HIT
Skin grafts and reattaching body parts
Route: Injection
Alprostadil
Tx: ED
Injectable prostaglandin (PGE1) leads to vasodilation when injected directly into penis
Mipomersen
Tx: hyperlipidemia
Antisense oligonucleotide
Mech: Binds to mRNA of ApoB
Prevents Apo from being synth
*(Apolipoprotein)*+cholesterol→VLDL
Must be given by injection
Ticlopidine
Tx: Anticoagulant
Mech: Platelet inhibitor
ADP receptor blocker on platelet
SE:
- Neutropenia-loss of neutrophils
- Agranulocytosis
Dabigatran
Tx: Anticoagulant
Mech: Direct thrombin inhibitor
Enzyme inhibitor
Route: Oral
Kinetics:
- Prodrug
- Onset w/in 1 hr
- P450 inhibitor may impact
SE-hemorhhage
Glyceryl Trinitrate (nitroglycerin) (GTN)
Tx: Angina
Mech:
GTN→NO→Act. guanylate cyclase→cGMP→vasodilation
Rapidly dilates all blood vessels, including coronary art.
Route: Given sublingually–1st pass effect
Effects last 30-60min
Rapid tolerance so cannot take continuously
SE:
- Hypotension
- Skin flushing
- Headache-opening blood vessels in brain, feel pulsing
*Nitroglycerin is unstable and explosive in some conditions
Icosapent
Tx: Hyperlipidemia
Mech: Inhibit enzyme responsible for Trig synth
Not clear though
Anagrelide
Tx: Anticoagulant
Mech: Platelet inhibitor
Platelet count reducer
Decreases platelet formation, maturation, and #
“-grel”s
Tx: Anticoagulant
Mech: Platelet inhibitor
ADP receptor blocker on platelet
Same as ticlopidine-diff is pharmacokinetics: rapid onset, shorter T1/2
Digoxin
Tx: CHF
Class: Cardiac glycoside
- Naturally occuring (foxglove and milk weed)
- Produced as protection for plant
Route: orally
Kinetics: long T1/2
Mech:
- When m stimulated, small influx of Ca→causes release of Ca into cell from SR→contraction
- In order for m to relax after contraction, Ca must be removed (Na and Ca pumped out, K pumped in)
- Digoxin inhibits NaK-ATPase
- Na remains high in cell→prevents loss of Ca
- High conc of Na inhibits the Na-Ca exchanger
- Net result: Ca remains high
- High Ca→greater contractility
Effects:
- Increases duration of contractile response
- Stimulates vagus n
- Anti-arrythmic effects
SE:
- Cardiac arrythmias
- CNS effects
- Yellow-green tinting of vision
- Hallucinations
- Activation of chemoreceptor trigger zone→severe nausea
- Effects enhanced in hypokalemia
- Cardiac glycosides bind and K site
- If less K outside of cell, more effective
Digoxin poisoning treated w/ anti-digoxin anti-bodies
“-rudin”s
Bivalirudin
Desirudin
Tx: Anticoagulant
Synthetic analogs of hirudin
Clinical use: when patient has HIT
Skin grafts and reattaching body parts
Route: Injection
Dronedarone
Tx: arrytmhias (Class III)
Mech: K+ channel blocker
Analog of amiodarone
Fewer SE-less efficacious
Metoprolol
Tx: arrythmias (Class II)
Mech: B1 blocker
More selective
SE:
- Bradycardia
- Hypotension
Abciximab
Tx: Anticoagulant
Mech: Platelet inhibitor
Fibrinogen receptor blocker on platelet (GPIIB/IIIA receptor)
Monoclonal antibody
Clinical use: Decrease white thrombi
Used for coronary operation
Route: IV
SE: Thromobocytopenia
Dobutamine
Tx: CHF
Class: Inotropic agents
Mech: Beta1 agonist
Effects: Increase force of contraction
Vorapaxar
Tx: Anticoagulant
Mech: Platelet inhibitor
Thrombin receptor blocker on platelet
SE: Use carefully w/ pts w/ history of intracranial bleeding
Olestra
Fake fat
SE: Butt leakage
“-xaban”s
Tx: Anticoagulant
Mech: Factor Xa inhibitor
Think -xaban=_Ban_s factor Xa
Route: Oral
Kinetics: Rapid onset
SE: Bleeding after spinal tap or spinal injurty
Fenofibrate
Tx: Hyperlipidemia
Mech: Bind to PPAR-peroxisome proliferation acting receptor
Effects
- Increase transcription of LPLase
- Decrease VLDL
- Decrease Trig.
SE:
- GI upset-nausea, vomiting
- Can displace warfarin from plasma binding sites
Verapamil
Tx: Arrythmias except vent. arrythmias (class IV)
Mech: Ca channel blockers
Increase refractory period
Aminocaproic acid
Tx: Hemostatic agent (enhance clotting)
Mech: Inhibits plasminogen activation
Enzyme inhibitor
Binds to plasminogen in plasma
Route: Oral or injection
Procainamide
Tx: All arrythmias (Class Ia)
- Also LA
Mech: Na channel blocker
- Like quinidine but does not get into CNS
- Quinidine:*
- Depresses all mm fxn
- Anti-cholinergic effects (antivagal effects)
- *Vagal innervation slows HR–Quinidine will speed it up
SE:
- Lupus like syndrome in slow acetylators
Omega 3 fatty acids
Tx: Hyperlipidemia
Mech: Inhibit enzyme responsible for Trig synth
Not clear though
Quinidine
Tx: All arrythmias (Class Ia)
Mech: Na channel blocker
- Depresses all mm fxn
- Anti-cholinergic effects (antivagal effects)
- *Vagal innervation slows HR–Quinidine will speed it up
SE:
- GI
- Nausea and vomiting
- Anorexia
- CNS
- Tinnitus
- Alterted color vision
Iomitapide
Tx: Hyperlipidemia
Mech: Inh assembly of VLDL in liver
Apolipoprotein+cholesterol→(X)→VLDL
Enzyme for assembly is also a transporter
SE: hepatotoxicity
Ezetimibe
Tx: Hyperlipidemia
Mech: Blocks cholesterol transport
SE: Flatulence
Niacin
aka Vit B3
aka Nicotinic acid
Tx: Hyperlipidemia
Mech:
- Inh. enzyme essential for VLDL synth
- May also bind to receptor that decreases VLDL synth
Effects:
- Decrease VLDL
- Increase HDL–strongest increase of any drug
SE:
- Cutaneous flushing and itching (prevented by aspirin)
- Increase uric acid–>gout
- Increase incidence of diabetes
“-statin”s
Lovastatin
Bunch of other -statins whose diff is pharmacokinetics
Tx: Hyperlipidemia
Mech:
- Lovastatin is prodrug
-
HMG CoA reductase inhibitor
- Rate limiting step in cell synth of their own cholesterol
- When cells can’t make own cholesterol→increase in LDL receptors→increase LDL uptake
Effects:
- Decrease LDL (25%)
- Decrease VLDL synth
SE:
- Myositis (muscle pain)
- At worst→rhabdomyolysis (muscle breakdown)
- Liver toxicity
- Teratogenic–preg. category X
- Some memory loss
Kinetics-metab by P450
Mexiletine
Tx: arrythmias (Class Ib)
Mech: Na channel blocker
Clinical use:
- Emergency tx of ventricular arrythmias
- Tx of ventricular tachycardia
Like lidocaine but can be given orally
Angina definition and general tx methods
Not enough BF to heart
Causes chest pain (m becomes anoxic)
We usually have chest pain after we work out b/c we need more O2
But if at rest it is unstable angina
Tx by increasing BF or decreasing O2 demand
Tx:
- Behavioral
- Diet
- Exercise
- Creates collateral circulation (more blood vessels) in heart
- Stop smoking
- Drugs
Amiodarone
Tx: arrytmhias (Class III)
DOC for cardiac arrest–most effective anti-arrythmic
Mech: K+ channel blocker
Acts like all 4 classes of anti-arrythmic
SE:
- Potentially fatal pulmonary fibrosis
- Replaces lung tissue w/ fiber composites
- Liver damage
- Corneal deposits-optic neuritis
- Deposits in skin-blue/gray skin coloration
- GI upset
*Iodine responsible for some deposits
Cilostazol
Tx: Anticoagulant
Mech: Platelet inhibitor
Inhibits phosphodiesterase
Inh. enzyme that breaks down cAMP
Increased cAMP→Decrease platelet agg.
Tranexamic acid
Tx: Hemostatic agent (enhance clotting)
Mech: Inhibits plasminogen activation
Enzyme inhibitor
Binds to plasminogen in plasma
“-parin” drugs excluding heparin
Enoxaparin
Dalteparin
Tx: Anticoagulant
Low molecular wt heparins-Partially purified heparin
Longer T1/2=4 hrs
More effect on Xa than thrombin
Less osteoporosis and HIT
More predictable dose-response
(Smaller so don’t bind as readily to lots of proteins)
More expensive
Not readily reversed by protamine sulfate
SE: spinal hematoma in pts who have had spinal tap or anesth.
Dipryridamole
Tx: Anticoagulant
Mech: Platelet inhibitor
Inhibits phosphodiesterase
Inh. enzyme that breaks down cAMP
Increased cAMP→Decrease platelet agg.
Tirofiban
Tx: Anticoagulant
Mech: Platelet inhibitor
Fibrinogen receptor blocker on platelet (GPIIB/IIIA receptor)
Clinical use: Decrease white thrombi
Used for coronary operation
Route: IV
SE: Thromobocytopenia
Hydroxyurea
Mech: Increase formation of fetal Hb (does not sickle)
SE: Mutagenic
Pregnancy category D
Nifedipine
Tx: Arrythmias except vent. arrythmias (class IV)
Mech: Ca channel blockers
Increase refractory period
Orlistat
Tx: Hyperlipidemia
Mech: Inh GI and pancreatic lipase
Decrease fat absorption from gut
SE: Loose stool
Sitostanol
Tx: Hyperlipidemia
Mech: Looks like cholesterol–blocks uptake
Hirudin
Tx: Anticoagulant–found in leech saliva
Mech: Directly inhibits thrombin
Enzyme inhibitor
Aspirin
Tx: Anticoagulant
Mech: Platelet inhibitor
COX (enzyme) inhibitor
Inhibits TXA2 synth
Decreases platelet aggregation
Propranolol
Tx: arrythmias (Class II)
Mech: B1 blocker
Decreases pacemaker firing rate
SE:
- Bradycardia
- Hypotension
- B2 effects-asthma
“Poetin” and “Pegin”
Epoietin alfa
Darbepoietin
Peginesatide
Tx: Anemia due to chronic renal failure or chemotherapy
Toxicities: Due to excess RBCs
- Increase BP
- Increase clotting
- MI
- Stoke
